As disclosed in U.S. Pat. No. 5,057,613, these compounds were previously known to show a dopamine betahydroxylase (DBH) inhibiting activity and to be useful in the treatment of hypertension at dosages of about 1 mg to 100 mg per kilogram body weight. Subsequent studies have shown that these compounds have a profound effect on the thyroid, rendering them useful for treating hyperthyroidism at doses equivalent to or lower than their blood pressure lowering dosages. Assays indicating the activity of compounds of this invention as DBH inhibitors and antihypertensive agents are described in U.S. Pat. No. 5,057,613, which is incorporated herein by reference.
It has now been discovered that the compounds of this invention are also potent antihyperthyroid agents. This activity is not normally associated with DBH inhibitors having antihypertensive activity. One compound combining antihyperthyroid activity with DBH inhibitory activity is methimazole (Tapazole.RTM., Lilly). Methimazole, 1-methyl-2-mercaptoimidazole, is administered for treatment of hyperthyroidism in dosages of 15-60 mg/day divided into 3 doses for administration at 8-hour intervals (Physicians' Desk Reference, 1992). Studies by Ray W. Fuller, et al., (Advances in Enzyme Regulation, 1977, V15, pp. 267-281), have shown that methimazole's DBH-inhibiting activity is less pronounced than that of methimazole analogs bearing larger 1-alkyl substituents in place of the methyl group, while the greatest DBH inhibition was measured for 1-cyclohexyl-2-mercaptoimidazole (CHMI) which showed only slight antithyroid activity.